{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:35:33Z","timestamp":1786977333491,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Abrocitinib is a Janus kinase (JAK) 1 selective inhibitor approved for the treatment of atopic dermatitis. Female reproductive tissues were unaffected in general toxicity studies, but an initial female rat fertility study resulted in adverse effects at all doses evaluated. A second rat fertility study was conducted to evaluate lower doses and potential for recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This second study had 4 groups of 20 females each administered abrocitinib (0, 3, 10, or 70\u2009mg\/kg\/day) 2\u2009weeks prior to cohabitation through gestation day (GD) 7. In addition, 2 groups of 20 rats (0 or 70\u2009mg\/kg\/day) were dosed for 3\u2009weeks followed by a 4\u2010week recovery period before mating. All mated females were evaluated on GD 14.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No effects were observed at \u226410\u2009mg\/kg\/day. At 70\u2009mg\/kg\/day (29x human exposure), decreased pregnancy rate, implantation sites, and viable embryos were observed. All these effects reversed 4\u2009weeks after the last dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Based on these data and literature on the potential role of JAK signaling in implantation, we hypothesize that these effects may be related to JAK1 inhibition and, generally, that peri\u2010implantation effects such as these, in the absence of cycling or microscopic changes in nonpregnant female reproductive tissues, are anticipated to be reversible.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.2345","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T04:23:20Z","timestamp":1715142200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Reversible effects on female rat fertility with abrocitinib, a Janus kinase 1 inhibitor"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2425-2603","authenticated-orcid":false,"given":"Christopher J.","family":"Bowman","sequence":"first","affiliation":[{"name":"Pfizer Research &amp; Development  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8328-7718","authenticated-orcid":false,"given":"Sarah N.","family":"Campion","sequence":"additional","affiliation":[{"name":"Pfizer Research &amp; Development  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8100-0701","authenticated-orcid":false,"given":"Natasha R.","family":"Catlin","sequence":"additional","affiliation":[{"name":"Pfizer Research &amp; Development  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Nowland","sequence":"additional","affiliation":[{"name":"Pfizer Research &amp; Development  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Stethem","sequence":"additional","affiliation":[{"name":"Pfizer Research &amp; Development  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaher A.","family":"Radi","sequence":"additional","affiliation":[{"name":"Pfizer Research &amp; Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg D.","family":"Cappon","sequence":"additional","affiliation":[{"name":"Pfizer Research &amp; Development  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1335.020"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0890-6238(96)00134-7"},{"key":"e_1_2_9_4_1","first-page":"149","volume-title":"Principles and practice of toxicologic pathology","author":"Bowman C. 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